Mutations in Myosin 5B in Children With Early-onset Cholestasis.

OBJECTIVES: Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. METHODS: Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. RESULTS: Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 µmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 µmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. CONCLUSIONS: We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.

Prediction of prolonged ventilator dependence in preterm infants.

Volutrauma is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Our aims were to identify risk factors in the first 24 h for prolonged ventilator dependence and assess volume delivery and carbon dioxide levels in infants with evolving BPD. A retrospective study was undertaken of 41 infants born at less than 32 weeks of gestational age (GA). A higher tidal volume, minute volume and resistance and a lower GA, birth weight and compliance were associated with a significantly higher risk of ventilator dependence at 28 days. The strongest relationships were with birth weight (area under the receiver operating characteristic curve, AUROC = 0.771) and GA (AUROC = 0.813). Tidal volume remained significantly higher after adjusting for GA in those who remained ventilator dependent at 28 days. The 18 who remained ventilator dependent at 28 days had increased mean carbon dioxide (PCO2) levels with increasing age from a mean of 41 mmHg in the first 24 h to 65 mmHg at 28 days PMA (p < 0.001). The increase in PCO2 occurred despite increases in peak inflation pressures (p < 0.001), tidal volumes (p = 0.002) and minute volumes (p < 0.001).Conclusion: These results suggest that initial volutrauma may contribute to the development of chronic ventilator dependence. What is Known: • In prematurely born infants, excessive tidal volumes are important in the pathogenesis of bronchopulmonary dysplasia (BPD), but a tidal volume that is too low will increase the risk of atelectasis, work of breathing and energy expenditure. What is New: • A high tidal volume in the first 24 h was associated with an increased risk of ventilator dependence at 28 days, which remained significant after adjusting for gestational age. Carbon dioxide levels significantly increased over the first month despite increased pressures and volumes in those who remained ventilator dependent.

Early reported rectal sensation predicts continence in anorectal anomalies.

BACKGROUND: Straining at stool is an automatic reflex in babies and implies the presence of rectal sensation. We hypothesised that early reported rectal sensation would predict future continence in children with anorectal anomalies. AIM OF THE STUDY: The aim of this study is to determine if early straining at stool was a useful predictor of future continence in infants born with high anorectal malformations. METHODS: A retrospective case note review of prospectively collected clinical information was performed with institutional review board approval. All patients with intermediate/high anorectal malformation operated on by a single surgeon from 1984 to 2010 were included. After stoma closure, parents were asked: The responses were noted within the first year of stoma closure and then all patients were followed up until they were at least 3 ½years old and continence could be assessed using the Krickenbeck outcome classification. Data were compared using Fisher's exact test and sensitivity, specificity and positive predictive value (PPV) were calculated. MAIN RESULTS: Forty-eight patients were included in the study. Sixteen (33%) were female (12 cloacal malformation, 3 rectovaginal fistula, 1 rectal atresia) and 32 (66%) were male (6 rectovesical fistulae, 22 rectourethral fistulae, 4 no fistula). Median follow-up was 9.7years (range 3.5-17.9). Twenty-one children were noted by their parents to exhibit early straining at stool after stoma closure. Twenty of them achieved long term continence. The sensitivity of early straining as a predictor for long term continence was 77%, specificity 95% and positive predictive value 95%. CONCLUSION: The presence of early rectal sensation reported by parents is a good predictor of long term continence. This allows more informed discussion with families in the early years of life.